In 1959, spontaneous autoantibody production was discovered in New Zealand mice. Subsequent studies demonstrated a striking similarity of New Zealand black mice to patients with idiopathic acquired hemolytic anemia and New Zealand black x white F1 hybrids to humans with systemic lupus erythematosus. Numerous experiments have indicated that genetic and/or viral interrelationships with lymphoid elements are critical for disease pathogenesis in mice. However, the precise role of the thymus and spleen and their respective subpopulations in the development of autoimmunity and lymphoproliferative disease remains unclear. It is proposed herein to create unique animal models to resolve these issues. These models are production of congenitally athymic (nude) New Zealand black (NZB), New Zealand white (NZW) and NZBxNZW F1 mice; and New Zealand mice congenic for the Xid gene of CBA/N. The natural history and immune responsiveness of these mutant colonies will be studied and compared with littermate controls. Further, specific experiments in transplantation and cell transfer of thymus and spleen from syngeneic mice of different serial ages will be designed to identify the relationships between alterations in lymphoid subpopulations with age and development of autoimmunity and lymphoproliferative disease.